Steroid receptor coactivator-1 can regulate osteoblastogenesis independently of estrogen

Mol Cell Endocrinol. 2017 Jun 15;448:21-27. doi: 10.1016/j.mce.2017.03.005. Epub 2017 Mar 7.

Abstract

Steroid receptor coactivator-1 (SRC-1), a well-studied coactivator of estrogen receptor (ER), is known to play an important and functional role in the development and maintenance of bone tissue. Previous reports suggest SRC-1 maintains bone mineral density primarily through its interaction with ER. Here we demonstrate that SRC-1 can also affect bone development independent of estrogen signaling as ovariectomized SRC-1 knockout (SRC-1 KO) mouse had decreased bone mineral density. To identify estrogen-independent SRC-1 target genes in osteoblastogenesis, we undertook an integrated analysis utilizing ChIP-Seq and mRNA microarray in transformed osteoblast-like U2OS-ERα cells. We identified critical osteoblast differentiation genes regulated by SRC-1, but not by estrogen including alkaline phosphatase and osteocalcin. Ex vivo primary culture of osteoblasts from SRC-1 wild-type and KO mice confirmed the role of SRC-1 in osteoblastogenesis, associated with altered ALPL levels. Together, these data indicate that SRC-1 can impact osteoblast function in an ER-independent manner.

Keywords: Bone; Estrogen receptor; NCOA1; SRC-1.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Alkaline Phosphatase / metabolism
  • Animals
  • Bone Density / drug effects
  • Cell Differentiation / drug effects
  • Cell Line, Tumor
  • Estrogens / pharmacology*
  • Humans
  • Mice, Knockout
  • Nuclear Receptor Coactivator 1 / metabolism*
  • Osteoblasts / cytology
  • Osteoblasts / drug effects
  • Osteoblasts / metabolism*
  • Osteogenesis*

Substances

  • Estrogens
  • Nuclear Receptor Coactivator 1
  • Alkaline Phosphatase